In recent years, during the ravages of COVID-19, a variety of vaccines have been developed and are now on the market. However, although these new vaccines have undergone various trials, there are still many unknown side effects. We report a case of a 30-year-old woman who presented with general weakness, sore throat, generalized skin rashes, symmetrical arthralgia, and persistent fever of up to 40 °C with onset 16 days after receiving the Moderna COVID-19 vaccine. Adult-onset Still’s disease (AOSD) was diagnosed according to Yamaguchi’s criteria after excluding the feasibility of infectious diseases, autoimmune diseases, and malignancies. In particular, her responses to glucocorticoids and naproxen were significant and inversely proportional to her use of empirical antibiotics in the initial stage of treatment. We studied some similar cases of AOSD, which also considered the adverse effects of COVID-19 vaccination and suggested the immunogenicity and possibility of inflammatory responses related to COVID-19 vaccination.